For certain applications of antiseptic disinfectants, a coloured marking of the treated surface (such as skin or mucosa) is desired, for example before a surgical intervention or during an operation.
Besides compositions based on the active ingredient PVP-iodine, which are already coloured brown-red on account of the coloration of the active ingredient, there are coloured skin antiseptics on the market, where the active ingredients are for example nonionic (e.g. Kodan® tincture forte coloured, with 45% by weight of 2-propanol, 10% by weight of 1-propanol, 0.2% by weight of 2-biphenylol, H2O2, E104, E110, E151). The group of cationic antiseptic active ingredients for skin antiseptics includes chlorhexidine digluconate (hereinbelow “chlorhexidine”), which has been successful on the US market in formulations with 70% 2-propanol (e.g. the product Chloraprep® from Carefusion, formerly Enturia). In principle, however, there are concerns regarding chlorhexidine-containing antiseptics, specifically on account of the possible formation of p-chloroaniline (carcinogenic, toxic) as one possible degradation product upon storage. Moreover, on account of the comparatively low efficacy of chlorhexidine, higher active ingredient concentrations are required in the product. On account of the high active ingredient concentrations in these products, for antiseptics based on chlorhexidine, any loss in efficacy upon adding small amounts of dyes is not a problem.
DE 41 37 548 A1 discloses antimicrobial active ingredient combinations based on acridine dyes (which have their own antimicrobial effect), optionally in combination with further antimicrobial active ingredients. Carcinogenic properties are discussed for acridine dyes; use in disinfectant preparations for application to the human skin is accordingly not possible.
DE 199 01 526 A1 discloses an antiseptic which comprises defined amounts of 1-propanol, 2-propanol and ethanol. Furthermore, the optional presence of dyes is provided. Problems due to the interaction of antiseptic active ingredients with specific dyes is not discussed in DE 199 01 526 A1.
DE 10 2007 030 416 A1 describes alcoholic antiseptics which comprise 50 or more % by weight of alcohol having 1 to 3 carbon atoms, dye and optionally further antimicrobial active ingredients. Besides a broad multitude of dyes, a broad multitude of optional antimicrobial additives is disclosed. However, compositions which obligatorily comprise 50 or more % by weight of alcohol are undesired.
WO2007/062306 A2 describes processes for coating surfaces. In this process, a composition which comprises antimicrobial agent is cured on the surface by means of heat, where the composition can comprise a dye. Typically, the surface is an inanimate surface (for example a medical device). The use of compositions for the antiseptic treatment of animate surfaces is not described.
WO2007/130981 A2 describes aqueous solutions of chlorhexidine and a cationic dye. However, chlorhexidine in antiseptics for use in the oral cavity turns the teeth and the tongue brownish. Also, after prolonged use, the sense of taste can be adversely affected. EP 2 499 913 A1 also deals with chlorhexidine-containing antiseptic solutions, and anionic dyes are proposed for their colouring.
WO97/46622 A1 describes the use of natural or nature-identical synthetic dyes for the marking or inking of materials. By way of example, mention is made of the temporary marking of operation areas using dye-containing desinfection solution or coloured pens on the skin. The fact that certain active ingredients of disinfectants have a remanence effect which must not be influenced by the dye used is not discussed in WO97/46622 A1.
WO03/015531 A2 describes a pharmaceutical formulation which comprises a dye and has a content of opiate.
DE 40 33 690 A1 discloses adducts of norbixin with water-soluble or water-dispersible proteins or branched-chain or cyclic polysaccharides. Norbixin is a carotenoid with two carboxylic acid groups obtained from annatto seeds. Bixin is the monomethyl ester of norbixin. The adducts are used for example for colouring milk. The colouring of surfaces by means of coloured disinfectants is not discussed.
WO2005/123013 A1 discloses the use of amino-substituted hydroxybenzophenone compounds for stabilizing the colour of cosmetic and dermatological preparations.
WO02/091832 A1 describes two-component disinfection systems, where the first component comprises chlorite and the second component comprises acid and optionally oxidizable dye. By adding α-olefinsulfonate, the generation of chlorine dioxide upon combining the two components is reduced, as a result of which the dye present is oxidatively attacked to a lesser extent and is available for marking disinfected areas. According to the teaching of WO02/091832 it is also not important that the remanence effect of an active ingredient is not adversely affected by an added dye. Moreover, the use of two-component disinfectants is complex and consequently not suitable for use in the hospital sector.
WO2006/028025 A1 describes antibacterial compositions with a content of special benzopyranones.
WO2006/077616 A1 deals with a system for the visualization of contaminated areas using a film with controlled release of coloured substances.
WO2007/100654 A2 discloses a method for controlling microorganisms in which a surface is coated with a removable composition forming an antimicrobial film.
WO2008/032212 A2 relates to coloured or colourable foamable compositions for topical applications where the coloration of the composition differs from that of the foam produced therefrom.
According to DE 38 31 920 A1, a photostable cosmetic composition for protecting the human epidermis against UV radiation is said to comprise a combination of bixin with fat-soluble UV-ray-absorbing compound.
WO2009/138890 A2 describes a wipe made of fibre material, where beads are included in the fibre material and the beads include an active ingredient. Upon wetting the beads, they break open and release the active ingredient.
WO2011/006263 A1 relates to coloured antibacterial compositions for mouth disinfection. The compositions can comprise dye.
EP 2 345 336 A1 teaches a dye composition which comprises a mixture of two special emulsifiers.
DE 10 2011 056 111 A1 relates to an emulsion with an aqueous phase and oil phase dispersed therein, with a dye being present in the oil phase. The dye is preferably a carotenoid, and the emulsifier in the aqueous phase is a saponin, which is used in combination with esters from plant lipid and food acid for emulsification.
U.S. Pat. No. 5,244,666 A describes surgical and wound disinfectants with a content of quaternary ammonium compound and dye.
WO02/082907 A1 describes complexes of antiseptics with dyes. By way of example, compositions with chlorhexidine are described which, as mentioned above, is undesired.
WO2004/083905 A2 describes an applicator for applying a liquid which is coloured in the applicator. For this purpose, in the applicator there is a glass ampoule filled with the liquid, and upon breaking open the ampoule the liquid flows through a porous element (such as a felt) which comprises dye. The dyed composition is then applied to the desired surface. A stability of a mixture of antiseptic active ingredient and dye is not an issue here, nor is the fact that the antiseptic active ingredient has to remain antimicrobially effective even upon prolonged contact with the dye.
According to WO2014/043354 A1 (US2014/0081222 A1), an antiseptic based on chlorhexidine or octenidine is applied with the help of a hydrophilic, solid (polyurethane) foam. According to WO2014/043199 A1 (US2014/0081221 A1), the solid (polyurethane) foam is hydrophobic. The antiseptic can be coloured or be coloured by dye present in the foam.
WO2009/058144 A1 discloses an antiseptic solution which comprises a micellar complex and a cationic antiseptic active ingredient, where the micellar complex consists of cationic auxiliary and anionic dye. Examples of cationic auxiliaries are quaternary ammonium compounds.
According to the teaching of WO2009/058144 A1, the cationic auxiliary is supposed to prevent an insoluble precipitate forming from the anionic dye and the cationic antiseptic active ingredient. In an alternative, a separate catonic auxiliary is added which forms the micellar complex with the anionic dye. Alternatively, it is possible to use a superstoichiometric amount of cationic antiseptic active ingredient (superstoichiometric with regard to the molar amount of anionic dye). Moreover, it was tested over a period of 24 hours whether precipitates result.
A stipulated comparatively large amount of cationic agent (namely cationic auxiliary and additionally cationic antiseptic agent, or alternatively a large amount of antiseptic active ingredient), however, is undesired. Moreover, testing over just 24 hours is not very meaningful. Since an applicator is used for applying the solution in which the disinfectant comes into contact with the dye dissolved out of a felt only for a comparatively short period, a stability of dye in contact with the antiseptic active ingredient over a prolonged period and a high remanence effect of the antiseptic active ingredient are not decisive according to the teaching of WO2009/058144 A1.
The medicament and surgical skin antiseptic Octeniderm® has hitherto been approved as a colourless product. It comprises 0.1% by weight of octenidine dihydrochloride (“octenidine” for short hereinbelow) as remanent active ingredient (and 30% by weight of 1-propanol, 45% by weight of 2-propanol, remainder: completely demineralized water). Octenidine is a quaternary ammonium compound of the imine type (cation) with chloride as anion and can be inhibited by the vast majority of anionic dyes in its antiseptic efficacy. Since Octeniderm® comprises only 0.1% octenidine, dyes added for colouring the skin in a relatively high concentration (up to 0.5% as in the case of products containing chlorhexidine) can lead to a long-term (up to 24 hours) significant reduction in the remanent effect of octenidine.
It has been found that the triphenylmethane dye Patent Blue V, despite its anionic character, shows no restriction of the efficacy of the octenidine in Octeniderm®. However, blue dyes are not accepted by the market on account of the poor visibility of the vessels under the skin.